Felipe Rodríguez de Castro

Drug-Resistant Pneumococcal Pneumonia: Clinical Relevance and Related Factors

A multicenter study of 638 cases of community-acquired pneumonia due to Streptococcus pneumoniae (SP-CAP) was performed to assess current levels of resistance. Of the pneumococcal strains, 35.7% had an minimum inhibitory concentration (MIC) of penicillin of > or =0.12 microg/mL (3 isolates had an MIC of 4 microg/mL), 23.8% had an MIC of erythromycin of 128 microg/mL, and 22.2% were multidrug resistant. Logistic regression determined that chronic pulmonary disease (odds ratio [OR], 1.44], human immunodeficiency virus infection (OR, 1.98), clinically suspected aspiration (OR, 2.12), and previous hospital admission (OR, 1.69) were related to decreased susceptibility to penicillin, and previous admission (OR, 1.89) and an MIC of penicillin of MIC > or =0.12 microg/mL (OR, 15.85) were related to erythromycin resistance (MIC, > or =1 microg/mL). The overall mortality rate was 14.4%. Disseminated intravascular coagulation, empyema, and bacteremia were significantly more frequent among patients with penicillin-susceptible SP-CAP. Among isolates with MICs of penicillin of > or =0.12 microg/mL, serotype 19 was predominant and was associated with a higher mortality rate. In summary, the rate of resistance to beta -lactams and macrolides among S. pneumoniae that cause CAP remains high, but such resistance does not result in increased morbidity.

Reaching Stability in Community-Acquired Pneumonia: The Effects of the Severity of Disease, Treatment, and the Characteristics of Patients

BACKGROUND The natural history of the resolution of infectious parameters in patients with community-acquired pneumonia (CAP) is not completely known. The aim of our study was to identify those factors related to host characteristics, the severity of pneumonia, and treatment that influence clinical stability. METHODS In a prospective, multicenter, observational study, we observed 1424 patients with CAP who were admitted to 15 Spanish hospitals. The main outcome variable was the number of days needed to reach clinical stability (defined as a temperature of <or=37.2 degrees C, a heart rate of <or=100 beats/min, a respiratory rate of <or=24 breaths/min, systolic blood pressure of >or=90 mm Hg, and oxygen saturation >or=90% or arterial oxygen partial pressure of >or=60 mm Hg). RESULTS The median time to stability was 4 days. A Cox proportional hazard model identified 6 independent variables recorded during the first 24 h after hospital admission related to the time needed to reach stability: dyspnea (hazard ratio [HR], 0.76), confusion (HR, 0.66), pleural effusion (HR, 0.67), multilobed CAP (HR, 0.72), high pneumonia severity index (HR, 0.73), and adherence to the Spanish guidelines for treatment of CAP (HR, 1.22). A second Cox model was performed that included complications and response to treatment. This model identified the following 10 independent variables: chronic bronchitis (HR, 0.81), dyspnea (HR, 0.79), confusion (HR, 0.61), multilobed CAP (HR, 0.84), initial severity of disease (HR, 0.73), treatment failure (HR, 0.31), cardiac complications (HR, 0.66), respiratory complications (HR, 0.77), empyema (HR, 0.57), and admission to the intensive care unit (HR, 0.57). CONCLUSIONS Some characteristics of CAP are useful at the time of hospital admission to identify patients who will need a longer hospital stay to reach clinical stability. Empirical treatment that follows guidelines is associated with earlier clinical stability. Complications and treatment failure delay clinical stability.

Mannose-binding lectin and mannose-binding lectin–associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults

BACKGROUND Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. Mannose-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) deficiencies are common primary immunodeficiencies the clinical penetrance of which remains controversial. MBL is a serum lectin that mediates phagocytosis and activates the lectin pathway of complement involving MASP-2. OBJECTIVE We sought to evaluate the significance of MBL deficiency (O/O genotypes) and insufficiency (O/O plus XA/O genotypes), as well as MASP-2 deficiency (D105G mutation), in the susceptibility to and severity and outcome of CAP in adults. METHODS MBL and MASP-2 serum levels, as well as lectin pathway activity with regard to MBL2 and MASP2 genotypes, were measured in healthy control subjects. For susceptibility, 848 patients with CAP, 1447 healthy control subjects, and a control group of 519 patients without relevant infectious diseases were studied in a case-control study. Severity and outcome were evaluated in a prospective study of the 848 patients. RESULTS We found similar frequencies of MBL2 and MASP2 alleles and genotypes among patients and control subjects. However, in a multivariate analysis MBL insufficiency was associated with the development of the most severe forms of sepsis (P = .007), acute respiratory failure (P = .009), multiorgan dysfunction syndrome (P = .036), intensive care unit admission (P = .020), and death (P = .003). CONCLUSION Our large study suggests that MBL plays a redundant role in human defenses against primary infection, at least in adults with CAP, and provides, for the first time, evidence that MBL insufficiency predisposes to higher severity and fatal outcome in patients with CAP, irrespective of the causal microorganisms.

Prevalence of latex allergy among greenhouse workers

ment regimens do not prevent this complication, and because it may recur, this case would not support the use of nonionic low contrast medium as a preventive measure for subsequent needed procedures. Although rare, acute pulmonary edema after administration of radiographic contrast media is potentially life-threatening. Ticeatment must be directed toward diuresis and the maintenance of adequate gas exchange. Acute pulmonary edema taust not be confused with the more typical bronchospastic ana, phylactoid reaction in order to avoid delay in starting appropriate therapy. ~ s case reinforces the need for a high index of suspicion for this problem in any patient experieneing acute dyspnea after a radiologic procedure with any of the eurrently available contrast media,

Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma

BACKGROUND Extended cervical mediastinoscopy (ECM) is a technique in the staging of bronchogenic carcinoma described first by Ginsberg in 1984. To update our experience we have prospectively evaluated our results on 106 patients who underwent the technique from 1985 to 1998. METHODS The ECM technique is performed once the operability of the patient has been evaluated, according to the computed tomography findings. The intervention is carried out at the same time as a standard cervical mediastinoscopy through the same incision following the same technique as previously published. The ECM is considered positive when metastatic nodes or tumor involvement directly in the paraaortic or subaortic regions is detected and confirmed histologically. Negative cases of ECM and positive cases of standard cervical mediastinoscopy are excluded from this study. A false-negative ECM is defined as the presence of infiltrated adenopathies at the paraortic level detected on postoperative histologic study. RESULTS We had performed ECM in 106 patients, and a total of 13 were subsequently excluded for the reasons stated above. Of the remaining cases, 26 were positive, 61 negative and 6 had false-negative results with no false-positive results. Sensitivity was 81.2%, specificity 100%, accuracy 93.3%, positive predictive value 100%, and negative predictive value 91%. There were no complications with the technique. CONCLUSIONS We conclude that ECM is a useful technique for staging bronchogenic carcinoma that allows samples to be taken from paraortic and subaortic regions with minimally invasive techniques.

Reduction of house dust mite allergens after dehumidifier use

It has been recognized that relative humidity is a key factor in mite popula t ion growth and allergen p roduc t ion? We under took a control led study to determine whether the levels o f mite allergen collected f rom mattresses decreased after dehumidifier use. The study was carried out in the Canary Islands, a subtropical area at sea level, where a prevalence o f 43% of allergic diseases (asthma, rhinitis, or both) and 48.5% of skin test reactivity to Dermatophagoides pteronyssinus has been r e p o r t e d ?

Association of HLA-DR11 with the anaphylactoid reaction caused by nonsteroidal anti-inflammatory drugs.

BACKGROUND Several HLA alleles have been associated with asthma induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The existence of HLA markers linked to other NSAID-induced reactions, such as cutaneous and anaphylactoid reactions, has not been established. OBJECTIVE The purpose of our work was to study the HLA-DRB1 and HLA-DQB1 alleles in patients with cutaneous and anaphylactoid reactions caused by NSAIDs. METHODS We have analyzed 114 HLA DRB1 and 26 HLA-DQB1 alleles in 21 patients with anaphylactoid reactions caused by NSAIDs, 47 patients who had exclusively cutaneous reactions during single-blind, placebo-controlled oral challenges with NSAIDs, and 167 tolerant control subjects (29 of whom had also had an IgE-mediated anaphylaxis to different agents). HLA-DRB1 and HLA-DQB1 alleles were typed by the polymerase chain reaction sequence-specific primers method with genomic DNA. RESULTS The frequency of HLA-DR11 alleles was 58.8% in the anaphylactoid reaction group, compared with 15.9% in the NSAID-tolerant healthy control subjects (OR, 7:3; 95% confidence interval, 2.8-19.0; P <.02) and 6.3% in the group of the patients with a tolerance for NSAIDs and with IgE-mediated anaphylaxis (OR, 18.75; 95% confidence interval, 4.3-81.1; P <.004). No differences were observed among HLA-DR11 alleles analyzed. There were no significant HLA-DQB1 associations with NSAID-induced anaphylactoid reactions. Patients with cutaneous reactions had HLA frequencies that did not differ significantly from the tolerant control subjects. CONCLUSION The HLA-DRB1*11 alleles showed a positive association with NSAID-induced anaphylactoid reactions.

The Fcγ receptor IIA-H/H131 genotype is associated with bacteremia in pneumococcal community-acquired pneumonia.

Objective: To assess the potential association of the functional polymorphism rs1801274 in the receptor IIa for the Fc portion of immunoglobin G (Fc&ggr;RIIa) gene (FCGR2A-H131R) with the susceptibility to and the severity of community-acquired pneumonia (CAP). Design: Multicenter prospective and observational study. Setting: Four university hospitals in Spain. Patients: FCGR2A-H131R polymorphism was determined in 1,262 patients with CAP and in 1,224 in the subject control group. Measurements and Main Results: Severe sepsis was recorded in 366 patients. No significant differences in genotype or allele frequencies were seen among patients with CAP or pneumococcal CAP (PCAP) and controls. Patients with bacteremic PCAP (B-PCAP) had significantly higher frequencies of FCGR2A-H/H131 genotypes than those with nonbacteremic PCAP (p = .00016, odds ratio = 2.9, 95% confidence interval 1.58–5.3). The differences remained significant when adjusting for pneumonia severity index, hospital of origin, and intensive care unit admission (p = .0012, odds ratio = 2.83, 95% confidence interval 1.51–5.32). B-PCAP was associated with a significantly higher severity of the disease, evaluated as sepsis severity (p = .000007, odds ratio = 4.40, 95% confidence interval 2.31–8.39), multiorgan dysfunction syndrome (0.00048, odds ratio = 3.29, 95% confidence interval 1.69–6.41), intensive care unit admission, acute renal failure, and acute respiratory distress syndrome. Conclusions: Our results do not support a role of FCGR2A-H131R polymorphism in susceptibility to CAP or PCAP. However, we provide the insight that homozygosity for FCGR2A-H131 predisposes B-PCAP, which was associated with higher severity in our study.

Genetic variability in the severity and outcome of community-acquired pneumonia.

BACKGROUND Several studies have investigated single nucleotide polymorphisms (SNP) in candidate genes associated with susceptibility, severity or outcome in patients with community-acquired pneumonia (CAP) with conflicting results. METHODS Multi-centre, prospective observational study. We studied 1162 white Spanish patients with CAP and 1413 controls. Severe forms of sepsis were recorded in 325 patients. Subjects were genotyped for the following polymorphisms: TNF -238 and -308, LTA +252, IL6 -174, IL1RN 86bp variable number of tandem repeats and TNFRSF1B+676 (TNFR2 M196R). RESULTS No significant differences in genotype or allele frequencies were seen among patients and controls. We did not find any association between TNF, LTA, IL6 and IL1RN polymorphisms with disease severity or outcome. Analysis of 28-day mortality showed a significant difference in the distribution of TNFRSF1B+676 G/T genotypes (p=0.0129). Sequential Kaplan-Meier survival analysis of TNFRSF1B+676 G/T polymorphism showed a protective role of the GT genotype. Cox regression analysis adjusted for age, gender, hospital of origin and comorbidities showed that patients with GT genotypes had lower mortality rates compared to patients with GG or TT genotypes (p=0.02; HR 0.53; 95% CI 0.31-0.90 for 90-day survival; p=0.01; HR 0.41; 95% CI 0.21-0.81 for 28-day survival and p=0.049; HR 0.48; 95% CI 0.23-0.997 for 15-day survival). CONCLUSIONS Our study does not support a role for the controversial studied polymorphisms of the TNF, LTA, IL6 and IL1RN genes in the susceptibility or outcome of CAP. A protective role of heterozygosity for the functionally relevant TNFRSF1B+676 polymorphism in the outcome of CAP was observed.

Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of β-lactam-resistant pneumococcal infections, the use of standard antipneumococcal β-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, β-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (β-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.